rs746215294

Variant names:

• chrX-68717255-A-G
• rs746215294
• NM_001142503.3:c.341A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001142503.3(STARD8):​c.341A>G​(p.His114Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,202,735 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 82 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.00018 (0 hom. 81 hem.)
• Consequence: STARD8 NM_001142503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51
• Publications: 1 publications found

Genes affected

STARD8 (HGNC:19161): (StAR related lipid transfer domain containing 8) This gene encodes a member of a subfamily of Rho GTPase activating proteins that contain a steroidogenic acute regulatory protein related lipid transfer domain. The encoded protein localizes to focal adhesions and may be involved in regulating cell morphology. This protein may also function as a tumor suppressor. [provided by RefSeq, Mar 2010]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04130736).
• BS2: High Hemizygotes in GnomAdExome4 at 81 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142503.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD8	NM_001142503.3	MANE Select	c.341A>G	p.His114Arg	missense	Exon 6 of 15	NP_001135975.1	Q92502-2
	STARD8	NM_001142504.3		c.101A>G	p.His34Arg	missense	Exon 5 of 14	NP_001135976.1	Q92502-1
	STARD8	NM_014725.5		c.101A>G	p.His34Arg	missense	Exon 5 of 14	NP_055540.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STARD8	ENST00000374599.8	TSL:1 MANE Select	c.341A>G	p.His114Arg	missense	Exon 6 of 15	ENSP00000363727.3	Q92502-2
	STARD8	ENST00000252336.10	TSL:1	c.101A>G	p.His34Arg	missense	Exon 5 of 14	ENSP00000252336.6	Q92502-1
	STARD8	ENST00000374597.3	TSL:1	c.101A>G	p.His34Arg	missense	Exon 5 of 14	ENSP00000363725.3	Q92502-1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 11 AN: 111547 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000379

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000170

Gnomad OTH AF: 0.000662

GnomAD2 exomes AF: 0.000249 AC: 41 AN: 164905 AF XY: 0.000365

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000385

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000236

Gnomad OTH exome AF: 0.00120

GnomAD4 exome AF: 0.000182 AC: 199 AN: 1091188 Hom.: 0 Cov.: 32 AF XY: 0.000227 AC XY: 81 AN XY: 357536

African (AFR) AF: 0.0000380 AC: 1 AN: 26324

American (AMR) AF: 0.0000290 AC: 1 AN: 34489

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19162

East Asian (EAS) AF: 0.00 AC: 0 AN: 30064

South Asian (SAS) AF: 0.000779 AC: 41 AN: 52599

European-Finnish (FIN) AF: 0.0000250 AC: 1 AN: 40057

Middle Eastern (MID) AF: 0.00486 AC: 20 AN: 4116

European-Non Finnish (NFE) AF: 0.000137 AC: 115 AN: 838549

Other (OTH) AF: 0.000436 AC: 20 AN: 45828

GnomAD4 genome AF: 0.0000986 AC: 11 AN: 111547 Hom.: 0 Cov.: 22 AF XY: 0.0000296 AC XY: 1 AN XY: 33729

African (AFR) AF: 0.00 AC: 0 AN: 30636

American (AMR) AF: 0.00 AC: 0 AN: 10623

Ashkenazi Jewish (ASJ) AF: 0.000379 AC: 1 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3519

South Asian (SAS) AF: 0.00 AC: 0 AN: 2573

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6133

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.000170 AC: 9 AN: 52994

Other (OTH) AF: 0.000662 AC: 1 AN: 1511

Alfa AF: 0.000260 Hom.: 1

Bravo AF: 0.000136

ExAC AF: 0.000132 AC: 16

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.70
DANN	Benign	0.45
DEOGEN2	Benign	0.0064	T
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.5
PrimateAI	Benign	0.34	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.044
Sift	Benign	0.41	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.32		Gain of solvent accessibility (P = 0.0074)
MVP		0.84
MPC		0.074
ClinPred		0.025	T
GERP RS		0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.049
gMVP		0.047
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs746215294; hg19: chrX-67937097;